The objective of the proposed research is to identify cellular mechanisms underlying associative learning and to relate these mechanisms to general principles of information processing by sensory systems. Building on the recent demonstration of activity-dependent associative plasticity in individual sensory neurons mediating afferent input for the tail withdrawal reflex in Aplysia, the proposed experiments will test the hypothesis that this associative plasticity is a mechanism for classical conditioning of tail withdrawal. Differential classical conditioning of tail withdrawal will be examined in a semi-intact preparation in which behavioral and cellular alterations in identified neurons within the reflex circuit can be measured simultaneously. Alterations both in the monosynaptic connections to identified tail motor neurons and in the electro-physiological properties of the sensory neuron soma will be measured. Both classes of assciative modification will be compared to associative plasticity produced by pairing intracellular activation of sensory neurons with application of the presumed reinforcing neuromodulator (serotonin) in both the semi-intact preparation and the isolated sensory neuron soma. The possible interactions of associatively specific activity-dependent neuromodulation with changes in membrane potential and lateral inhibition will be examined in an attempt to identify sensory processes that may contribute to more complex features of associative learning such as sequence specificity, overshadowing, and blocking. By precisely defining conditioning and test stimuli in the semi-intact preparation and relating the effects of conditioning with these stimuli to the details of cellular associations measured under analogous conditions in the isolated soma, the groundwork for an eventual quantitative model of associative processing in this sensory system will be laid. Since learning is one of the fundamental capabilities of most if not all nervous systems, these studies may shed light on general mechanisms involved in both the normal function and some of the dysfunctions of the human brain.